Format

Send to

Choose Destination
J Biol Inorg Chem. 2015 Oct;20(7):1081-95. doi: 10.1007/s00775-015-1290-2. Epub 2015 Sep 1.

Evaluation of fluorophore-tethered platinum complexes to monitor the fate of cisplatin analogs.

Author information

1
Laboratory of Cell Biology, National Cancer Institute, Center for Cancer Research, National Institutes of Health, 37 Convent Drive, Rm. 2108, Bethesda, MD, 20892, USA.
2
Imaging Probe Development Center, National Institutes of Health, Rockville, MD, USA.
3
Advanced Mass Spectrometry Facility, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
4
Laboratory of Cell Biology, National Cancer Institute, Center for Cancer Research, National Institutes of Health, 37 Convent Drive, Rm. 2108, Bethesda, MD, 20892, USA. mgottesman@nih.gov.

Abstract

The platinum drugs cisplatin, carboplatin, and oxaliplatin are highly utilized in the clinic and as a consequence have been extensively studied in the laboratory setting, sometimes by generating fluorophore-tagged analogs. Here, we synthesized two Pt(II) complexes containing ethane-1,2-diamine ligands linked to a BODIPY fluorophore, and compared their biological activity with previously reported Pt(II) complexes conjugated to carboxyfluorescein and carboxyfluorescein diacetate. The cytotoxicity and DNA damage capacity of Pt-fluorophore complexes was compared to cisplatin, and the Pt-BODIPY complexes were found to be more cytotoxic with reduced cytotoxicity in cisplatin-resistant cells. Microscopy revealed a predominately cytosolic localization, with nuclear distribution at higher concentrations. Spheroids grown from parent and resistant cells revealed penetration of Pt-BODIPY into spheroids, and retention of the cisplatin-resistant spheroid phenotype. While most activity profiles were retained for the Pt-BODIPY complexes, accumulation in resistant cells was only slightly affected, suggesting that some aspects of Pt-fluorophore cellular pharmacology deviate from cisplatin.

KEYWORDS:

Accumulation; Platinum; Resistance; Trafficking

PMID:
26323351
PMCID:
PMC5035150
DOI:
10.1007/s00775-015-1290-2
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center